Background: Increased risk of fractures and osteoporosis have been associated with the use of antiretroviral drugs.\r\nThere is a paucity of prospective evaluations of bone markers after the initiation of drugs currently recommended\r\nto treat HIV infection and results on the evolution of these markers are conflicting. Lastly, the effect of tenofovir on\r\n1,25-(OH)2 vitamin D is uncertain.\r\nMethods: We performed a prospective study on the evolution of bone markers, parathormone and 1,25-(OH)2 vitamin\r\nD before and after standard antiretroviral regimens. This was a sub-study of a trial conducted in antiretroviral-na�¯ve\r\npatients randomized to tenofovir emtricitabine in combination with either atazanavir/ritonavir (ATV/r) or efavirenz\r\n(EFV). Follow-up lasted 48 weeks. The following bone markers were analyzed: C-terminal cross-laps (CTx), osteocalcin\r\n(OC), osteoprotegerin (OPG), and receptor activator of nuclear factor B ligand (RANKL). Mixed-factorial analysis of\r\nvariance with random-coefficient general linear model was used to compare their trends over time and linear\r\nmultivariable regression was performed with a backward selection method to assess predictors of their variations from\r\nbaseline to week 48. Trends of parathormone and 1,25-(OH)2 vitamin D were also evaluated.\r\nResults: Seventy-five patients were studied: 33 received EFV and 42 ATV/r. Significant increases were found for all\r\nmarkers except for RANKL. There was a significant direct association between CTx and OC increases. Multivariable\r\nanalysis showed that higher glomerular filtration rate (estimated through cystatin C clearance) predicted greater\r\nOPG increase, while older age, higher HIV RNA at baseline and use of ATV/r predicted greater CTx increase. A\r\nsignificant increase of parathormone accompanied the evolution of the study markers. 1,25-(OH)2 vitamin D\r\nremained stable, though a seasonality variation was demonstrated.\r\nConclusions: These data demonstrate CTx increase (bone resorption marker) corresponding to OC increase (bone\r\nformation marker) early upon HAART initiation. Moreover, predictors of bone marker increases have been\r\nsuggested, possibly indicating that a stricter monitoring of bone health and pro-active interventions are needed in\r\nolder patients, those with higher HIV RNA, prescribed ATV/r rather than EFV, and with decreased renal function at\r\nbaseline. Further studies are needed to clarify the mechanisms responsible for up-regulation of bone turnover\r\nmarkers, as well as to understand if and what markers are best correlated or predictive of pathological fractures.
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